Synthesis, characterization and an extensive biological evaluation of 5-​[2-​(methylthio)​ethyl]​-​3-​(2-​propen-​1-​yl)​-​2-​thioxo-4-​imidazolidinone

Abstract

Ever since their discovery, hydantoins have attracted huge attention due to their intriguing properties, vast chemical diversity and potential, as well as their broad spectra of biological activity. The wide set of their biological activity includes antimicrobial, antitumor, antiandrogen, anticonvulsant, antiteratogenic activity, etc. They are also used in the treatment of cachexia, psoriasis, wounds in general and also as muscle relaxants. There are many synthetic routes to hydantoins and some of them involve amino acids. As rigorous chemical conditions are not required, these reactions can be manifested in physiological conditions too, especially in the cases when protein consumption is increased and thus hydantoins have been isolated from urine. With all this in mind, elucidation of biological implications of hydantoins gains importance. In this study, an amino acid derived 2-thiohydantoin, 5​[2-​(methylthio)​ethyl]​​3-​(2​propen​1​yl)​​2-​thioxo-4​imidazolidinone, has been synthesized and fully characterized by NMR and IR spectroscopy, as well as X-ray crystallography. An extensive antimicrobial study has been carried out on ten bacterial isolates (Grampositive and Gram-negative), as well as on five fungal isolates. Cytotoxicity has been tested on the cell lines of the normal lung fibroblasts, as well as breast, colon and lung tumor cell lines. Ultimately, a fish embryo toxicity (FET) assay has been carried out in vivo on the zebrafish model, testing for lethal and teratogenic effects and cardiotoxicity. Based on the found biological activity in previously mentioned assays, a determination of therapeutic potential has been carried out to show whether the compound is toxic in antimicrobial and anticancer doses.